Joan Massagué

Joan Massagué is the Director of the Sloan Kettering Institute and Chairman of the Cancer Biology and Genetics Program at Memorial Sloan Kettering Cancer Center, and is universally recognized as the world's leading authority on TGF-β (transforming growth factor beta) signaling in cancer biology. Massagué's laboratory at MSKCC has spent three decades dissecting how the TGF-β signaling pathway functions in both normal tissue homeostasis and cancer — a paradoxical pathway that suppresses tumor growth in early stages but actively promotes metastasis and immune evasion in advanced disease. His group biochemically purified the TGF-β receptor system and identified the canonical SMAD transcription factors as the primary intracellular effectors of TGF-β signals, a discovery that defined one of the most fundamental signaling axes in biology. The pathway Massagué characterized mediates growth arrest, apoptosis, and differentiation in normal cells. In advanced cancers, however, TGF-β signaling is co-opted to drive epithelial-mesenchymal transition (EMT), immunosuppression, production of osteolytic factors for bone metastasis, and induction of cancer stem cell properties. Massagué's laboratory demonstrated how cancer cells acquire selective resistance to TGF-β's tumor-suppressive effects while retaining its pro-metastatic functions — a phenomenon with profound therapeutic implications. His research on organ-specific metastasis has been equally foundational. Using genomic approaches, he identified gene expression signatures that enable breast cancer cells to metastasize specifically to bone (involving CXCR4, CTGF, osteopontin), to lung (EREG, MMP1, ANGPTL4), and to brain (COX2, HBEGF, ST6GALNAC5). This work explained the "seed and soil" specificity of metastasis at a molecular level. Massagué has also made seminal discoveries in cancer dormancy — why disseminated cancer cells remain latent at distant sites for years or decades before reactivating as overt metastases. His laboratory identified DEC2, LIFR, and other factors that impose dormancy programs on disseminated tumor cells, opening avenues for preventing metastatic recurrence.

Joan Massagué 是纪念斯隆凯特琳癌症中心斯隆凯特琳研究所所长，是公认的TGF-β信号在癌症生物学中作用的全球领军权威。他的实验室从生化角度鉴定了TGF-β受体系统，并发现SMAD转录因子是TGF-β信号的主要胞内效应子，定义了生物学中最基本的信号轴之一。 他的研究阐明了癌细胞如何在保留TGF-β促转移功能的同时获得对其肿瘤抑制效果的选择性耐药，并识别了使乳腺癌细胞特异性转移到骨、肺和脑的基因表达特征。他在癌症休眠方面的开创性工作揭示了播散性肿瘤细胞在远处位点保持潜伏的分子机制。